The progression of malignant diseases can in some cases be monitored by measuring serum levels of appropriate tumor markers. Numerous immunological assays for the detection of blood-borne tumor antigens have been developed, and of these, the most useful can be categorized into two broad groups. One group is based on actively secreted protein or glycoprotein antigens, such as alpha-fetoprotein and prostate specific antigen, and the second, on heavily glycosylated, high molecular weight antigens, such as carcinoembryonic antigen or the mucin-like antigens which are released by unknown mechanisms from a variety of tumor types.
Some varieties of cancers such as cancers of the breast--which are one of the largest classes of malignant disease in women--are not readily monitored using existing serological tests. Several potential serum markers for breast cancer are described in the literature. Ceriani et al, PNAS (1982) 79:5420-5424 describe mammary epithelial antigens which apparently are elevated in serum of patients with disseminated breast cancer. Burchell, J., et al, Int J Cancer (1984) 34: 763-768 have described monoclonal antibodies which detect high molecular weight mucin-like antigens elevated in patient serum. Hayes, D. F., J Clin Invest (1985) 75: 1671-1678 also describes a monoclonal antibody that recognizes a high molecular weight mammary epithelial antigen present in elevated amounts in the plasma of breast cancer patients. See also Papsidero, L. D., et al, Cancer Res (1984) 44: 4653-4657; TaylorPapadimitriou, J., et al, Int J Cancer (1981) 28: 17-28, and U.S. Pat. No. 4,522,918. In the absence of structural data for epitopes recognized by these antibodies it is impossible to determine the relationship between them or the antibodies used in the present invention. In any event, none of the previously described antibodies has been used as a basis for a widely accepted clinical assay.
Copending U.S. patent application Ser. No. 690,750 filed 11 Jan. 1985, now U.S. Pat. No. 4,753,894, describes a series of anti-breast cancer monoclonal antibodies. Those antibodies were identified based on their ability to bind selectively to human breast cancer cells and their efficacy as immunotoxins for breast cancer when conjugated to ricin A chain. The monoclonal antibodies that are used in the present invention methods are included in that series. The application states that the antibodies may be used in immunoassays to detect or monitor breast cancer. The specific assays it mentions are cellular rather than serological. The application does not suggest that any of the antigens recognized by the antibodies might be blood-borne breast cancer markers. The present invention is based on the finding that two of the antibodies described in that application recognize the same antigen or associated antigens which is/are elevated in breast cancer patient sera.